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作 者:孙凤杰[1] 佟德民[2] 李娟[1] 邓长柏[1] SUN Feng-jie;TONG De-min;LI Juan;DENG Chang-bo(Department of Neonatology,the Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510700,China;Department of Traditional Chinese Medicine,the Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510700,China)
机构地区:[1]广州医科大学附属第五医院新生儿科,广东广州510700 [2]广州医科大学附属第五医院中医科,广东广州510700
出 处:《基础医学与临床》2019年第6期810-815,共6页Basic and Clinical Medicine
基 金:广东省科技计划项目(20140212);广州医科大学博士启动项目(2013C59);广州市医药卫生科技项目(20151A011094,20161A011091)
摘 要:目的了解肌细胞增强子-2C(MEF-2C)在妊娠糖尿病(GDM)胎鼠心脏发育过程中的表达,探讨其在GDM胎鼠心脏发育异常中的作用机制。方法将雌鼠随机分为对照组(n=24),GDM组(n=30):孕后腹腔注射2%链脲佐菌素(STZ)40 mg/kg,柠檬酸组(n=30):孕后每只动物腹腔注射柠檬酸-柠檬酸钠液(2%链脲佐菌素溶剂)40 mg/kg,胰岛素组(n=30):采用2%STZ建立GDM模型鼠后于孕后72 h(血糖12~15 mmol/L)每天皮下注射给予中效胰岛素(诺和锐30R)20 U/kg,采尾静脉血监测血糖及称重,并分别于孕12、15、19 d 3个时间点剖腹获取胎鼠心脏组织:观察胎鼠心脏发育情况,HE染色观察心脏结构,免疫组化检测心脏组织MEF-2C蛋白,荧光定量PCR检测MEF-2C mRNA,Western blot检测MEF-2C蛋白。结果各组MEF-2C蛋白表达呈动态变化:孕12 d可见表达,孕15 d表达最高,孕19 d表达下降;与对照组相比,GDM组MEF-2C mRNA及MEF-2C蛋白的表达下降(P<0.05)。结论妊娠糖尿病胎鼠心脏发育异常率显著增高,MEF-2C与GDM胎鼠心脏发育异常可能存在相关性。Objective To investigate the expression of myocyte-specific enhancer factor 2 C(MEF-2 C) during cardiac development of gestational diabetes mellitus(GDM)’fetal rats, and to explore its mechanism. MethodsAdult Sprague-dawley(SD) female rats were randomly divided into control group(n=24), GDM group(n=30) were treated by intraperitoneal injection of 2% streptozotocin(STZ) 40 mg/kg body weight after determining the pregnancy, citric acid group(n=30) were intraperitoneally injected with citric acid-sodium citrate buffer solution after determining the pregnancy, insulin group(n=30) were subcutaneously injected with intermediate-acting insulin(NovoMix 30 R, 20 U/kg·d) when blood sugar level was 12~15 mmol/L after 72 h of GDM model rats. The changes of blood sugar level and the changes of body weight were recorded in pregnant rats of each group. The cardiac tissues of fetal rats in each group were obtained by caesarean section at embryonic day E12,E15 and E19.Then these cardiac tissues of fetal rats were observed and were the histopathological changes of cardiac development under microscope with HE staining;changes in the mRNA expression of MEF-2 C by RT-qPCR;changes in the expression of MEF-2 C protein by immunohistochemistry and Western blot. Results Dynamic variation of MEF-2 C protein level was observed in these group: expression of MEF-2 C protein in the cardiac tissue was found in E12 and it significantly increased on E15, but it decreasd on E19. Compared with control group, mRNA level and protein content of MEF-2 C in GDM group were decreased(P<0.05). Conclusions The abnormal rate of cardiac development in GDM group is significantly increased. MEF-2 C is potentially associated with cardiac dysplasia in GDM fetal rats.
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